Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice

Int J Mol Sci. 2020 Feb 9;21(3):1153. doi: 10.3390/ijms21031153.

Abstract

Ovarian cancer (OC) is one of the deadliest cancers among women contributing to high risk of mortality, mainly owing to delayed detection. There is no specific biomarker for its detection in early stages. However, recent findings show that over-expression of specificity protein 1 (Sp1) is involved in many OC cases. The ubiquitous transcription of Sp1 apparently mediates the maintenance of normal and cancerous biological processes such as cell growth, differentiation, angiogenesis, apoptosis, cellular reprogramming and tumorigenesis. Sp1 exerts its effects on cellular genes containing putative GC-rich Sp1-binding site in their promoters. A better understanding of the mechanisms underlying Sp1 transcription factor (TF) regulation and functions in OC tumorigenesis could help identify novel prognostic markers, to target cancer stem cells (CSCs) by following cellular reprogramming and enable the development of novel therapies for future generations. In this review, we address the structure, function, and biology of Sp1 in normal and cancer cells, underpinning the involvement of Sp1 in OC tumorigenesis. In addition, we have highlighted the influence of Sp1 TF in cellular reprogramming of iPSCs and how it plays a role in controlling CSCs. This review highlights the drugs targeting Sp1 and their action on cancer cells. In conclusion, we predict that research in this direction will be highly beneficial for OC treatment, and chemotherapeutic drugs targeting Sp1 will emerge as a promising therapy for OC.

Keywords: Sp1; cellular reprogramming; ovarian cancer; therapeutics approach; transcription factor.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Cycle
  • Cellular Reprogramming
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Molecular
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Sp1 Transcription Factor / analysis
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*

Substances

  • Sp1 Transcription Factor
  • Sp1 protein, human